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1.
Int J Mol Sci ; 22(22)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34830230

RESUMO

Phosphorus (P) is an essential macronutrient for plant growth and development. Among adaptive strategies of plants to P deficiency, increased anthocyanin accumulation is widely observed in plants, which is tightly regulated by a set of genes at transcription levels. However, it remains unclear whether other key regulators might control anthocyanin synthesis through protein modification under P-deficient conditions. In the study, phosphate (Pi) starvation led to anthocyanin accumulations in soybean (Glycine max) leaves, accompanied with increased transcripts of a group of genes involved in anthocyanin synthesis. Meanwhile, transcripts of GmCSN5A/B, two members of the COP9 signalosome subunit 5 (CSN5) family, were up-regulated in both young and old soybean leaves by Pi starvation. Furthermore, overexpressing GmCSN5A and GmCSN5B in Arabidopsis thaliana significantly resulted in anthocyanin accumulations in shoots, accompanied with increased transcripts of gene functions in anthocyanin synthesis including AtPAL, AtCHS, AtF3H, AtF3'H, AtDFR, AtANS, and AtUF3GT only under P-deficient conditions. Taken together, these results strongly suggest that P deficiency leads to increased anthocyanin synthesis through enhancing expression levels of genes involved in anthocyanin synthesis, which could be regulated by GmCSN5A and GmCSN5B.

2.
J Hazard Mater ; : 127720, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34810010

RESUMO

Phosphate (P) minerals and phosphate solubilizing fungi (PSF) play essential roles in lead (Pb) immobilization, but their roles in driving Pb bioavailability and ecological risks in red soil remains poorly understood. In this study, the inoculation of P. oxalicum and TCP successfully enhanced available P (AP) and urease concentrations in artificially Pb contaminated red soil. Combined P. oxalicum and TCP inoculation significantly reduced Pb bioavailability, bioaccessibility, leachability and mobility by increasing soil AP concentration and forming stable Pb-P compounds during the 21-day experiment. Soil AP and Pb bioavailability play an important role in shifting soil microbial communities induced by co-occurrence of P. oxalicum and TCP. Combined P. oxalicum and TCP could notably promote the relative abundances of predominant soil genus to enhance microbial resistance to soil Pb. Likewise, coexistence of P. oxalicum and TCP showed the highest biomass and better branch root development of Pb-stressed in lettuces (Lactuca sativa L.) in pot experiment, and significantly reduced up to 88.1% of Pb translocation from soil to root over control. The reductions of Pb translocation and accumulation in root in P. oxalicum + TCP treatment could enhance the oxidase activities and alleviate the oxidative damages of H2O2 and O2.- in shoot tissues. Our study provided strong evidence to use PSF associated with P materials for the stable and eco-friendly soil Pb remediation.

3.
Mitochondrial DNA B Resour ; 6(12): 3396-3397, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790873

RESUMO

This study determined the complete mitochondrial genome of Formosania galericula (Cypriniformes: Gastromyzontidae) from Zhejiang, China, for the first time. The complete mitochondrial genome of F. galericula was sequenced to be 16,555 bp in length. The genome contained 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, two central non-coding regions (the control region and the origin of light strand replication), identical to most other vertebrates. Phylogenetic analysis highly supported that F. galericula was close to Crossostoma lacustre and the genus Vanmanenia fish. However, F. galericula was not firstly clustered with Formosania chenyiyui but after the genus Vanmanenia fish. These data would explain the evolutionary mechanisms and biogeography of the family Gastromyzontidae and is helpful for the conservation of genetics and stock evaluation for F. galericula.

4.
Ecotoxicol Environ Saf ; 227: 112880, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34655883

RESUMO

Phosphorus (P) containing minerals are identified as effective Pb stabilizers in soil, while their low solubility limit the Pb immobilization efficiency. In this work, the combination of phosphate solubilizing fungi (PSF) Penicillium oxalicum and tricalcium phosphate (TCP) was constructed and applied to improve Pb immobilization stabilities in medium and soils. P. oxalicum+ TCP could significantly improve Pb2+ removal to above 99% under different TCP/Pb2+ and pH values. TCP and P. oxalicum could remarkably immobilize Pb by ion exchange, and PbC2O4 precipitation or surface adsorption, respectively. While the enhanced Pb immobilization in P. oxalicum+ TCP was explained by stronger Pb2+ interaction with tryptophan protein-like substances in extracellular polymeric substance, and the formation of the most stable Pb-phosphate compound hydroxypyromorphite (Pb5(PO4)3OH). Toxicity characteristic leaching procedure test showed that only 0.91% of Pb2+ was leachable in P. oxalicum+ TCP treatment, significantly lower than that in P. oxalicum (2.90%) and TCP (7.52%) treatments. In addition, the lowest soil exchangeable Pb fraction (37.1%) and the highest available soil P (88.0 mg/kg) were both found in P. oxalicum+ TCP treatment. By synergistically forming stable Pb-containing products, thus the combination of PSF and P minerals could significantly improve Pb2+ immobilization and stability in soils.


Assuntos
Penicillium , Poluentes do Solo , Fosfatos de Cálcio , Matriz Extracelular de Substâncias Poliméricas/química , Chumbo , Fosfatos/análise , Solo , Poluentes do Solo/análise
5.
Plant J ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587329

RESUMO

Phosphorus (P) deficiency adversely affects nodule development as reflected by reduced nodule fresh weight in legume plants. Though mechanisms underlying nodule adaptation to P deficiency have been studied extensively, it remains largely unknown which regulator mediates nodule adaptation to P deficiency. In this study, GUS staining and quantitative reverse transcription-PCR analysis reveal that the SPX member GmSPX5 is preferentially expressed in soybean (Glycine max) nodules. Overexpression of GmSPX5 enhanced soybean nodule development particularly under phosphate (Pi) sufficient conditions. However, the Pi concentration was not affected in soybean tissues (i.e., leaves, roots, and nodules) of GmSPX5 overexpression or suppression lines, which distinguished it from other well-known SPX members functioning in control of Pi homeostasis in plants. Furthermore, GmSPX5 was observed to interact with the transcription factor GmNF-YC4 in vivo and in vitro. Overexpression of either GmSPX5 or GmNF-YC4 significantly upregulated the expression levels of five asparagine synthetase-related genes (i.e., GmASL2-6) in soybean nodules. Meanwhile, yeast one-hybrid and luciferase activity assays strongly suggested that interactions of GmSPX5 and GmNF-YC4 activate GmASL6 expression through enhancing GmNF-YC4 binding of the GmASL6 promoter. These results not only demonstrate the GmSPX5-GmNF-YC4-GmASL6 regulatory pathway mediating soybean nodule development, but also considerably improve our understanding of SPX functions in legume crops.

6.
Bioelectrochemistry ; 142: 107895, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34364026

RESUMO

Microbial electrochemical snorkel (MES) is a short-circuited microbial fuel cell applicable to water treatment that does not produce energy but requires lower cost for its implementation. Few reports have already described its water treatment capabilities but no deeper electrochemical analysis were yet performed. We tested various materials (iron, stainless steel and porous graphite) and configurations of snorkel in order to better understand the rules that will control in a wetland the mixed potential of this self-powered system. We designed a model snorkel that was studied in laboratory and on the field. We confirmed the development of MES by identifying anodic and cathodic parts, by measuring the current between them and by analyzing microbial ecology in laboratory and field experiments. An important application is denitrification of surface water. Here we discuss the influence of nitrate on its electrochemical response and denitrification performances. Introducing nitrate caused the increase of the mixed potential of MES and of current at a potential value relatively more positive than for nitrate-reducing biocathodes described in the literature. The major criteria for promoting application of MES in artificial wetland dedicated to mitigation of non-point source nitrate pollution from agricultural water are considered.

7.
Plant Physiol Biochem ; 167: 222-234, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34371392

RESUMO

Phosphorus (P) deficiency is considered as a major constraint on crop production. Although a set of adaptative strategies are extensively suggested in soybean (Glycine max) to phosphate (Pi) deprivation, molecular mechanisms underlying reversible protein phosphorylation in soybean responses to P deficiency remains largely unclear. In this study, isobaric tags for relative and absolute quantitation, combined with liquid chromatography and tandem mass spectrometry analysis was performed to identify differential phosphoproteins in soybean roots under Pi sufficient and deficient conditions. A total of 427 phosphoproteins were found to exhibit differential accumulations, with 213 up-regulated and 214 down-regulated. Among them, a nitrate reductase, GmNR4 exhibiting increased phosphorylation levels under low Pi conditions, was further selected to evaluate the effects of phosphorylation on its nitrate reductase activity and subcellular localization. Mutations of GmNR4 phosphorylation levels significantly influenced its activity in vitro, but not for its subcellular localization. Taken together, identification of differential phosphoproteins reveled the complex regulatory pathways for soybean adaptation to Pi starvation through reversible protein phosphorylation.


Assuntos
Fosfatos , Soja , Regulação da Expressão Gênica de Plantas , Fosfatos/metabolismo , Fosforilação , Raízes de Plantas/metabolismo , Soja/metabolismo
8.
Mitochondrial DNA B Resour ; 6(9): 2741-2742, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447889

RESUMO

This study determined the mitochondrial genome of Sinobdella sinensis (Synbranchiformes: Mastacembelidae) from China's Qiantang River for the first time. The mitochondrial genome of S. sinensis was sequenced to be 16,543 bp in length, larger than S. sinensis from China's Yangtze River. The genome contains 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, two central non-coding regions (the control region and the origin of light strand replication), identical to most other vertebrates. Phylogenetic analysis highly supported that S. sinensis from China's Qiantang River was different from other Mastacembelus fish. However, it showed a close relationship with Macrognathus aculeatus. These data would explain the evolutionary mechanisms and biogeography of the family Mastacembelidae and is helpful for the conservation of genetics and stock evaluation for S. sinensis.

9.
J Membr Biol ; 254(5-6): 513-529, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34297135

RESUMO

In different large-scale clinic outcome trials, sodium (Na+)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na+ gradient to drive other Na+-dependent transporters, the possible role of the sodium-potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored.

10.
Small ; 17(32): e2101495, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34213822

RESUMO

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l-Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H2 O2 generated during PDT to oxidize Arg-ADP to NO and l-citrulline, without affecting singlet oxygen (1 O2 ) production. The combination of 1 O2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.


Assuntos
Infecções Bacterianas , Fotoquimioterapia , Infecções Bacterianas/tratamento farmacológico , Humanos , Peptídeos , Fármacos Fotossensibilizantes/uso terapêutico , Cicatrização
11.
Arch Microbiol ; 203(6): 3657-3665, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33993326

RESUMO

Glycyrrhiza uralensis Fisch is a widely cultivated traditional Chinese medicine plant. In the present study, culture-independent microbial diversity analysis and functional prediction of rhizosphere microbes associated with wild and cultivated G. uralensis Fisch plant (collected from two locations) were carried. Soil physicochemical parameters were tested to assess their impact on microbial communities. A total of 4428 OTUs belonging to 41 bacterial phyla were identified. In general, cultivated sample sites were dominated by Actinobacteria whereas wild sample sites were dominated by Proteobacteria. The alpha diversity analysis showed the observed species number was higher in cultivated soil samples when compared with wild soil samples. In beta diversity analysis, it was noticed that the weighted-unifrac distance of two cultivated samples was closer although the samples were collected from different regions. Functional annotation based on PICRUST and FAPROTAX showed that the nitrogen metabolism pathway such as nitrate reduction, nitrogen fixation, nitrite ammonification, and nitrite respiration were more abundant in rhizosphere microorganisms of wild G. uralensis Fisch. These results also correlate in redundancy analysis results which show correlation between NO3--N and wild samples, which indicated that nitrogen nutrition conditions might be related to the quality of G. uralensis Fisch.


Assuntos
Glycyrrhiza uralensis/microbiologia , Plantas Medicinais/microbiologia , Rizosfera , Glycyrrhiza uralensis/crescimento & desenvolvimento , Glycyrrhiza uralensis/metabolismo , Fixação de Nitrogênio , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , Solo
12.
J Bone Oncol ; 29: 100369, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34036039

RESUMO

Background: Targeted therapy has been established as the standard-of-care for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Among patients with advanced lung cancer, 30-40% have bone metastases (BoM) at first diagnosis. However, little is known on the clinical characteristics and prognostic factors of BoM in patients with NSCLC harboring EGFR mutations. Methods: Treatment-naive patients with advanced NSCLC harboring EGFR mutations who were prescribed tyrosine kinase inhibitors (TKIs) were screened and enrolled between June 2009 and April 2019 from West China Hospital. Patients were dichotomized according to whether they had BoM. The demographic characteristics, gene mutation status and therapeutic efficacy, including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), were collected. Results: A cohort of 604 patients were enrolled. The BoM group had worse PFS (11.7 vs. 14.0 months, HR = 0.73, p = 0.00013) and OS (32.8 vs. 46.1 months, HR = 0.54, p < 0.0001) compared with the non-BoM group. No significant differences were observed in disease control rate (p = 0.407) or ORR (p = 0.537) between the two groups. The metastatic sites in the two groups exhibited obvious differences. In multivariate analysis, BoM was found to be an independent factor of worse prognosis. Conclusion: BoM was identified as an independent inferior prognostic factor for EGFR-TKI treatment, and may have complex biological implications.

13.
Int J Mol Sci ; 22(7)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801629

RESUMO

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling. To examine a possible effect of endogenous concentrations of CTS on cardiac structure and function in vivo, we compared mice expressing the naturally resistant Na/K-ATPase α1 and age-matched mice genetically engineered to express a mutated Na/K-ATPase α1 with high affinity for CTS. In this model, total cardiac Na/K-ATPase activity, α1, α2, and ß1 protein content remained unchanged, and the cardiac Na/K-ATPase dose-response curve to ouabain shifted to the left as expected. In males aged 3-6 months, increased α1 sensitivity to CTS resulted in a significant increase in cardiac carbonylated protein content, suggesting that ROS production was elevated. A moderate but significant increase of about 15% of the heart-weight-to-tibia-length ratio accompanied by an increase in the myocyte cross-sectional area was detected. Echocardiographic analyses did not reveal any change in cardiac function, and there was no fibrosis or re-expression of the fetal gene program. RNA sequencing analysis indicated that pathways related to energy metabolism were upregulated, while those related to extracellular matrix organization were downregulated. Consistent with a functional role of the latter, an angiotensin-II challenge that triggered fibrosis in the α1r/rα2s/s mouse failed to do so in the α1s/sα2s/s. Taken together, these results are indicative of a link between circulating CTS, Na/K-ATPase α1, ROS, and physiological cardiac hypertrophy in mice under baseline laboratory conditions.


Assuntos
Glicosídeos Cardíacos/química , Coração/fisiologia , Miocárdio/enzimologia , ATPase Trocadora de Sódio-Potássio/genética , Angiotensina II/farmacologia , Animais , Cardiomegalia/patologia , Modelos Animais de Doenças , Ecocardiografia , Coração/efeitos dos fármacos , Masculino , Camundongos , Mutação , Ouabaína/farmacologia , Isoformas de Proteínas , RNA-Seq , Espécies Reativas de Oxigênio , Transdução de Sinais/efeitos dos fármacos
14.
Comput Methods Programs Biomed ; 202: 106004, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662804

RESUMO

BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a highly contagious virus spreading all around the world. Deep learning has been adopted as an effective technique to aid COVID-19 detection and segmentation from computed tomography (CT) images. The major challenge lies in the inadequate public COVID-19 datasets. Recently, transfer learning has become a widely used technique that leverages the knowledge gained while solving one problem and applying it to a different but related problem. However, it remains unclear whether various non-COVID19 lung lesions could contribute to segmenting COVID-19 infection areas and how to better conduct this transfer procedure. This paper provides a way to understand the transferability of non-COVID19 lung lesions and a better strategy to train a robust deep learning model for COVID-19 infection segmentation. METHODS: Based on a publicly available COVID-19 CT dataset and three public non-COVID19 datasets, we evaluate four transfer learning methods using 3D U-Net as a standard encoder-decoder method. i) We introduce the multi-task learning method to get a multi-lesion pre-trained model for COVID-19 infection. ii) We propose and compare four transfer learning strategies with various performance gains and training time costs. Our proposed Hybrid-encoder Learning strategy introduces a Dedicated-encoder and an Adapted-encoder to extract COVID-19 infection features and general lung lesion features, respectively. An attention-based Selective Fusion unit is designed for dynamic feature selection and aggregation. RESULTS: Experiments show that trained with limited data, proposed Hybrid-encoder strategy based on multi-lesion pre-trained model achieves a mean DSC, NSD, Sensitivity, F1-score, Accuracy and MCC of 0.704, 0.735, 0.682, 0.707, 0.994 and 0.716, respectively, with better genetalization and lower over-fitting risks for segmenting COVID-19 infection. CONCLUSIONS: The results reveal the benefits of transferring knowledge from non-COVID19 lung lesions, and learning from multiple lung lesion datasets can extract more general features, leading to accurate and robust pre-trained models. We further show the capability of the encoder to learn feature representations of lung lesions, which improves segmentation accuracy and facilitates training convergence. In addition, our proposed Hybrid-encoder learning method incorporates transferred lung lesion features from non-COVID19 datasets effectively and achieves significant improvement. These findings promote new insights into transfer learning for COVID-19 CT image segmentation, which can also be further generalized to other medical tasks.


Assuntos
COVID-19 , Processamento de Imagem Assistida por Computador , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Tomografia Computadorizada por Raios X , Algoritmos , Bases de Dados Factuais , Humanos , SARS-CoV-2
15.
Biology (Basel) ; 10(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671192

RESUMO

Phosphorus (P) is a vital element in biological molecules, and one of the main limiting elements for biomass production as plant-available P represents only a small fraction of total soil P. Increasing global food demand and modern agricultural consumption of P fertilizers could lead to excessive inputs of inorganic P in intensively managed croplands, consequently rising P losses and ongoing eutrophication of surface waters. Despite phosphate solubilizing microorganisms (PSMs) are widely accepted as eco-friendly P fertilizers for increasing agricultural productivity, a comprehensive and deeper understanding of the role of PSMs in P geochemical processes for managing P deficiency has received inadequate attention. In this review, we summarize the basic P forms and their geochemical and biological cycles in soil systems, how PSMs mediate soil P biogeochemical cycles, and the metabolic and enzymatic mechanisms behind these processes. We also highlight the important roles of PSMs in the biogeochemical P cycle and provide perspectives on several environmental issues to prioritize in future PSM applications.

16.
Sci Total Environ ; 770: 145362, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33736381

RESUMO

Phosphorus removal by algae-based biotechnology can be achieved through algal assimilation, surface adsorption, or abiotic precipitation. However, there are still unavailable how these phosphorus removal processes were affected by nanoparticles in wastewater. Here, we employed a non-targeted metabolomic approach to reveal the impact of silver nanoparticles (AgNPs) on the phosphorus assimilation by a unicellular green alga Chlorella vulgaris F1068 (C. vulgaris F1068). Results showed that AgNPs mostly inhibited total phosphorus (TP) removal by the algal assimilation, with TP removal efficiency being reduced by 66.2% (with 0.20 mg/L AgNPs) of the control (without AgNPs). Metabolomics analysis also indicated that AgNPs disturbed metabolic responses related to phosphorus assimilation. AgNPs inhibited phospholipid metabolism which included inositol phosphate metabolism and phosphatidylinositol signaling system (downregulation of glycerol-3-phosphate and myo-inositol, as well as upregulation of serine). Metabolites related to phosphorus assimilation products were impacted through downregulation of guanine, glutamine, alanine, and aspartic acid, as well as upregulation of succinic acid, thereby impeding the algal assimilation of phosphorus. Moreover, perturbation of glutathione metabolism induced by oxidative stress stimulated the alteration of membrane state (upregulation of glycine). These findings contribute to a molecular-scale perspective of nanoparticles on algae-based biotechnology in phosphorus removal.


Assuntos
Chlorella vulgaris , Nanopartículas Metálicas , Metabolômica , Fósforo , Prata
17.
Carbohydr Polym ; 257: 117636, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541661

RESUMO

Development of multifunctional antibacterial agent with long-lasting antibacterial activity and biofilm ablation performance is significant for the effective treatment of bacterial infections. Here, by utilizing the electrostatic interaction between sulfonated chitosan (SCS) and Ag+ and chitosan (CS), and the sodium borohydride reduction method, a versatile antibacterial agent (AgNPs@CS/SCS) capable of generating silver nanoparticles (AgNPs) in-situ and long-acting slow-release Ag+ was developed. AgNPs@CS/SCS has a good physiological stability and can long-acting slow-release of Ag+ due to the pH-dependent Ag+ release behavior of AgNPs. Noteworthy, AgNPs@CS/SCS can exert both excellent short- and long-term antibacterial and biofilm ablation activity. Importantly, it also exhibits superior antibacterial activity in the treatment of implant infections, accompanied by good biocompatibility. Together, this study suggest that AgNPs@CS/CSC is indeed a versatile antibacterial agent, and is expected to provide an effective treatment modality for implant infections in the clinic settings.


Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas/química , Nanogéis/química , Prata/química , Biofilmes/crescimento & desenvolvimento , Preparações de Ação Retardada/química , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Eletricidade Estática
18.
Med Image Anal ; 67: 101821, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33049579

RESUMO

There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.


Assuntos
Neoplasias Renais , Tomografia Computadorizada por Raios X , Estudos Transversais , Humanos , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem
19.
Adv Healthc Mater ; 10(8): e2001850, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314663

RESUMO

Hypoxia and hypoxia induced overexpression of vascular endothelial growth factor (VEGF) not only seriously affects the treatment effects of photodynamic therapy (PDT) but also promotes tumor metastasis. Herein, an alternating irradiation strategy (referred to as alternate use of low/high dose of light [ALHDL] irradiation)-driven combination therapy of PDT and RNA interference (RNAi) is developed to synergistically inhibit tumor growth and metastasis. A cationic amphipathic peptide (ALS) served as a carrier in the co-delivery system of photochlor (HPPH) and siVEGF (ALSH/siVEGF). At the beginning of ALHDL-driven ALSH/siVEGF treatment, short-term LDL irradiation can facilitate the tumor penetration, cellular uptake, and endosome escape of ALSH/siVEGF. Moreover, accompanied by HDL-mediated rapid cell apoptosis and LDL-mediated efficient VEGF silencing, the joint use of PDT and RNAi achieved remarkable antitumor effects both in vitro and in vivo. Importantly, benefited from the excellent performance of ALHDL in slowing the rapid deterioration of the anoxic environment of tumors, and ALSH/siVEGF treatment-mediated highly improved VEGF silencing efficacy and inhibitory effect on angiogenesis, the liver and lung metastases of HeLa cells have been successfully suppressed. Together, this study clearly indicates that ALHDL-driven combination therapy of PDT and RNAi is a highly effective modality for inhibition of tumor growth and metastasis.


Assuntos
Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Células HeLa , Humanos , Camundongos , Camundongos Nus , Fármacos Fotossensibilizantes , Interferência de RNA , RNA Interferente Pequeno , Fator A de Crescimento do Endotélio Vascular/genética
20.
PLoS One ; 15(12): e0244065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332475

RESUMO

Tissue fibrosis is a significant health issue associated with organ dysfunction and failure. Increased deposition of collagen and other extracellular matrix (ECM) proteins in the interstitial area is a major process in tissue fibrosis. The microRNA-29 (miR-29) family has been demonstrated as anti-fibrotic microRNAs. Our recent work showed that dysregulation of miR-29 contributes to the formation of cardiac fibrosis in animal models of uremic cardiomyopathy, whereas replenishing miR-29 attenuated cardiac fibrosis in these animals. However, excessive overexpression of miR-29 is a concern because microRNAs usually have multiple targets, which could result in unknown and unexpected side effect. In the current study, we constructed a novel Col1a1-miR-29b vector using collagen 1a1 (Col1a1) promoter, which can strategically express miR-29b-3p (miR-29b) in response to increased collagen synthesis and reach a dynamic balance between collagen and miR-29b. Our experimental results showed that in mouse embryonic fibroblasts (MEF cells) transfected with Col1a1-miR-29b vector, the miR-29b expression is about 1000 times less than that in cells transfected with CMV-miR-29b vector, which uses cytomegalovirus (CMV) as a promoter for miR-29b expression. Moreover, TGF-ß treatment increased the miR-29b expression by about 20 times in cells transfected with Col1a1-miR-29b, suggesting a dynamic response to fibrotic stimulation. Western blot using cell lysates and culture media demonstrated that transfection of Col1a1-miR-29b vector significantly reduced TGF-ß induced collagen synthesis and secretion, and the effect was as effective as the CMV-miR-29b vector. Using RNA-sequencing analysis, we found that 249 genes were significantly altered (180 upregulated and 69 downregulated, at least 2-fold change and adjusted p-value <0.05) after TGF-ß treatment in MEF cells transfected with empty vector. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using GAGE R-package showed that the top 5 upregulated pathways after TGF-ß treatment were mostly fibrosis-related, including focal adhesion, ECM reaction, and TGF-ß signaling pathways. As expected, transfection of Col1a1-miR-29b or CMV-miR-29b vector partially reversed the activation of these pathways. We also analyzed the expression pattern of the top 100 miR-29b targeting genes in these cells using the RNA-sequencing data. We identified that miR-29b targeted a broad spectrum of ECM genes, but the inhibition effect is mostly moderate. In summary, our work demonstrated that the Col1a1-miR-29b vector can be used as a dynamic regulator of collagen and other ECM protein expression in response to fibrotic stimulation, which could potentially reduce unnecessary side effect due to excessive miR-29b levels while remaining an effective potential therapeutic approach for fibrosis.


Assuntos
Embrião de Mamíferos/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Regulação da Expressão Gênica , MicroRNAs/biossíntese , RNA-Seq , Animais , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Embrião de Mamíferos/patologia , Matriz Extracelular/genética , Matriz Extracelular/patologia , Fibroblastos/patologia , Fibrose , Camundongos , MicroRNAs/genética
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